SonoVue®
A quality product from Bracco Imaging
As a result of many years of research and development conducted within Bracco, SonoVue® is a second-generation ultrasound contrast agent designed and optimized with regard to the resistance to pressure. The research has led to the selection of SF6, a gas with a low solubility in blood for the gaseous phase of the microbubbles and to a phospholipidic monolayer for the shell1, 2, 3.
SonoVue® was first approved in the European Union under the centralised procedure on 26 March 2001 and is currently marketed in 36 countries worldwide.
Today SonoVue® can boast more than 1,000 peer review journal articles in the life sciences4.
Physicochemical Characteristics
| ready-to-use suspension / vial | 5 ml |
| number of microbubbles / ml suspension | approx. 2 · 108 |
| gas content (SF 6) / ml suspension | 8 μl |
| mean diameter of microbubbles | approx. 2,5 μm |
| size range of microbubbles | 1 - 11 μm (90% < 6 μm, 99% <11 μm) |
| osmolality | approx. 290 mOsmol / Kg |
| viscosity | < 2 mPa · s |
| pH-value | 4,5 - 7,5 |
| stability after preparation | 6 hours |
Presentation
SonoVue® is presented as a kit. The needleless kit includes all the necessary material for
SonoVue® preparation:
- 5 ml saline 0.9% pre-filled syringe
- a minispike
- a vial containing gas and lyophilized powder.
Important Safety Information on SonoVue® (8 microlitres/ml powder and solvent for dispersion for injection) Use in Critically ill Patients
SonoVue® (8 microlitres/ml powder and solvent for dispersion for injection) is an ultrasound contrast agent consisting of a suspension of tiny microbubbles (most microbubbles between 2 and 9 microns) with a unique structure made of an inert gas, sulphur hexafluoride, and a phospholipid shell that provides stability and prevents microbubble coalescence. When injected intravenously, SonoVue® strongly enhances the echogenicity of blood, which results in an improved signal-to-noise ratio.
Important New Safety Information
Following an evaluation of the benefits and risks of SonoVue® use in critically ill patients made to by the Committee on Human Medicinal Products (CHMP) of the European Medicines Agency (EMA), the decision was made to:
- delete the contraindications for SonoVue® use in patients with recent acute coronary syndrome or clinically unstable ischaemic cardiac disease, including: evolving or ongoing myocardial infarction, typical angina at rest within last 7 days, significant worsening of cardiac symptoms within last 7 days, recent coronary artery intervention or other factors suggesting clinical instability (for example, recent deterioration of ECG, laboratory or clinical findings), acute cardiac failure, Class III/IV cardiac failure, or severe rhythm disorders;
- to insert SonoVue® use information on these patient populations into the Special Warnings and Precautions for Use section of the Product Information.
Since its launch in 2001, four (4) cases of severe cardiac arrhythmia occurred following concomitant administration of SonoVue® and the direct-acting, inotropic agent dobutamine. Of note, these 4 cases occurred in patients with either ongoing myocardial infarction, or other factors suggesting clinical instability, acute cardiac failure, or severe rhythm disorders, where the use of dobutamine is specifically contraindicated. One case, occurred in a patient with dilated cardiomyopathy and severe heart failure. This patient experienced ventricular fibrillation and cardiac arrest during the stress-echo procedure; the adverse events were considered related to the administration of dobutamine by the reporter. In the further clinical course, the patient had multiple cardiac arrests and developed subsequent cardiac and multi-organ-failure. She died 19 days after the reported events.
In view of these rare events and the frequent use of dobutamine for stress echocardiographic procedures, the CHMP also decided to make sure SonoVue® is not used in combination with dobutamine in those patients for which the use of this pharmacologic stressor is contraindicated.
Therefore, the CHMP decided to add the following contraindication to the Product Information of SonoVue®:
"SonoVue® should not be used in combination with dobutamine in patients with conditions suggesting cardiovascular instability where dobutamine is contraindicated".
In summary:
- SonoVue® is no longer contraindicated in patients with recent acute coronary syndrome or clinically unstable ischaemic cardiac disease.
- Prescribers may use SonoVue® in this patient population using extreme caution, after a careful risk/benefit assessment and with close monitoring of vital signs during and after administration.
- SonoVue® should not be used in combination with dobutamine in patients with conditions suggesting cardiovascular instability where dobutamine is contraindicated.
To provide SonoVue® users and prescribers with this new important safety information, Bracco has agreed upon with EMA and sent out a "Dear Healthcare Professional Communication" (DHPC). This letter is intended to minimise any potential risk for the use of SonoVue® in critically ill patients, which may particularly benefit from more accurate diagnostic information obtained after administration of SonoVue®.
The original DHCP letter is attached.
Further Information
SonoVue® is approved for use in:
- Echocardiography
SonoVue® is a transpulmonary echocardiographic contrast agent for use in patients with suspected or established cardiovascular disease to provide opacification of cardiac chambers and enhance left ventricular endocardial border delineation.
- Doppler of macrovasculature
SonoVue® increases the accuracy in detection or exclusion of abnormalities in cerebral arteries and extracranial carotid or peripheral arteries by improving the Doppler signal to noise ratio.
SonoVue® increases the quality of the Doppler flow image and the duration of clinically useful signal enhancement in portal vein assessment.
- Doppler of microvasculature
SonoVue® improves display of the vascularity of liver and breast lesions during Doppler sonography, leading to more specific lesion characterisation.
Call for reporting
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via their national reporting system.
Company Contact Points
Suspected adverse reactions should also be reported to Bracco International BV: braccodsu@bracco.com
Fax: +39-02-21772766
Phone: +39-02-21772327
For further inquiries concerning the information contained in this communication please contact Professional Services:
Services.ProfessionalEurope@bracco.com
Please download full Prescribing Information in the "Prescribing information" menu point above.
Indications
SonoVue® is for use with ultrasound imaging to enhance the echogenicity of the blood, which results in an improved signal to noise ratio5.
Echocardiography
SonoVue® is a transpulmonary echocardiographic contrast agent for use in patients with suspected or established cardiovascular disease, to provide opacification of cardiac chambers and enhance left ventricular endocardial border delineation5.
Doppler of macrovasculature
SonoVue® increases the accuracy in detection or exclusion of abnormalities in cerebral arteries and extracranial carotid or peripheral arteries by improving the Doppler signal to noise ratio.
SonoVue® increases the quality of the Doppler flow image and the duration of clinically useful signal enhancement in portal vein assessment5.
Doppler of microvasculature
SonoVue® improves display of the vascularity of liver and breast lesions during Doppler sonography, leading to more specific lesion characterisation5.
Special focus on liver and cardiac
SonoVue® in focal liver lesion characterization:
- excellent efficacy results comparable to CT and MRI 6, 7, 8, 9, 10
SonoVue® for guidance, monitoring and follow-up of percutaneous thermal ablation:
- precise real-time visualization of needle positioning during enhancement phase with most accurate lesion depiction11
- precise needle targeting of small lesions due to depiction of micro-circulation and parenchymal blood flow11
- immediate assessment of ablation treatment results11, 12, 13
- assessment of local recurrence/complete necrosis during the follow-up11, 12, 13
SonoVue® for endocardial border delineation:
- baseline echocardiography significantly underestimates left ventricular volumes compared to cine ventriculography and cardiac MRI14
- contrast echocardiography is particularly useful when a reproducible and accurate measurement of left ventricular function is needed15
1) Design of an ultrasound contrast agent for myocardial perfusion.
Schneider M.Echocardiography. 2000 Aug;17(6 Pt 2):S11-6. Review.
2) BR1: a new ultrasonographic contrast agent based on sulfur hexafluoride-filled microbubbles.
Schneider M., Arditi M., Barrau MB., Brochot J., Broillet A., Ventrone R., Yan F.Invest Radiol. 1995 Aug;30(8):451-7.
3) Characteristics of SonoVue®.
Schneider M.Echocardiography. 1999 Oct;16(7, Pt 2):743-746.
4) PubMed database
5) SonoVue® SPC
6) Contrast enhanced ultrasound for the characterization of focal liver lesions – Diagnostic accuracy in clinical practice (DEGUM multicenter trial)
Strobel D., Seitz K., Blank W., Schuler A., Dietrich C., von Herbay A., Friedrich-Rust M., Kunze G., Becker D., Will U., Kratzer W., Albert FW., Pachmann C., Dirks K., Strunk H., Greis C., Bernatik T.Ultraschall Med. 2008 Oct;29(5):499-505. doi: 10.1055/s-2008-1027806.
7) Contrast-Enhanced Ultrasound (CEUS) for the characterization of focal liver lesions - prospective comparison in clinical practice: CEUS vs. CT (DEGUM multicenter trial). Parts of this manuscript were presented at the Ultrasound
Dreiländertreffen 2008, DSeitz K., Strobel D., Bernatik T., Blank W., Friedrich-Rust M., Herbay Av., Dietrich CF., Strunk H., Kratzer W., Schuler A.Ultraschall Med. 2009 Aug;30(4):383-9. doi: 10.1055/s-0028-1109673. Epub 2009 Aug 17.
8) Contrast-enhanced ultrasound (CEUS) for the characterization of focal liver lesions in clinical practice (DEGUM Multicenter Trial): CEUS vs. MRI--a prospective comparison in 269 patients.
Seitz K., Bernatik T., Strobel D., Blank W., Friedrich-Rust M., Strunk H., Greis C., Kratzer W., Schuler A.Ultraschall Med. 2010 Oct;31(5):492-9. doi: 10.1055/s-0029-1245591. Epub 2010 Jul 22.
9) Prospective Multicenter Trial Evaluating a Novel Method of Characterizing Focal Liver Lesions Using Contrast-Enhanced Sonography.
Leen E., Ceccotti P., Kalogeropoulou C., Angerson WJ., Moug SJ., Horgan PG.AJR Am J Roentgenol. 2006 Jun;186(6):1551-9.
10) Real-time contrast-enhanced ultrasound in the evaluation of focal liver lesions: diagnostic efficacy and economical issues from a French multicentric study.
Tranquart F., Correas JM., Ladam Marcus V., Manzoni P., Vilgrain V., Aube C., Elmaleh A., Chami L., Claudon M., Cuilleron M., Diris B., Garibaldi F., Lucidarme O., Marion D., Beziat C., Rode A., Tasu JP., Trillaud H., Bleuzen A., Le Gouge A., Giraudeau B., Rusch E.J Radiol. 2009 Jan;90(1 Pt 2):109-22. French.
11) Monitoring RF ablation.
Solbiati L., Tonolini M., Cova L.Eur Radiol. 2004 Oct;14 Suppl 8:P34-42.
12) Is contrast-enhanced US alternative to spiral CT in the assessment of treatment outcome of radiofrequency ablation in hepatocellular carcinoma?
Ricci P., Cantisani V., Drudi F., Pagliara E., Bezzi M., Meloni F., Calliada F., Erturk SM., D'Andrea V., D'Ambrosio U., Passariello R.Ultraschall Med. 2009 Jun;30(3):252-8. doi: 10.1055/s-2008-1027727. Epub 2009 Mar 11.
13) Comparison of contrast enhanced ultrasound and contrast enhanced CT or MRI in monitoring percutaneous thermal ablation procedure in patients with hepatocellular carcinoma: a multi-center study in China.
Lu MD., Yu XL., Li AH., Jiang TA., Chen MH., Zhao BZ., Zhou XD., Wang JR.Ultrasound Med Biol. 2007 Nov;33(11):1736-49. Epub 2007 Jul 16.
14) Assessment of systolic left ventricular function: a multi-centre comparison of cineventriculography, cardiac magnetic resonance imaging, unenhanced and contrast-enhanced echocardiography.
Hoffmann R., von Bardeleben S., ten Cate F., Borges AC., Kasprzak J., Firschke C., Lafitte S., Al-Saadi N., Kuntz-Hehner S., Engelhardt M., Becher H., Vanoverschelde JL.Eur Heart J. 2005 Mar;26(6):607-16. Epub 2004 Dec 17.
15) The clinical applications of contrast echocardiography.
Olszewski R., Timperley J., Szmigielski C., Monaghan M., Nihoyannopoulos P., Senior R., Becher H.Eur J Echocardiogr. 2007 Jun;8(3):S13-23. Review. Erratum in: Eur J Echocardiogr. 2007 Oct;8(5):308. Cezary, Szmigielski [corrected to Szmigielski, Cezary]; Nihoyannopoulis, Petros [corrected to Nihoyannopoulos, Petros].
Preparation of SonoVue®
SonoVue® is supplied as a kit containing a vial with the phospholipids (lyophilisate) in a sulphur hexafluoride atmosphere, a prefilled syringe with physiological saline solution (0.9% saline solution) and a Mini-Spike transfer system.
The suspension must be reconstituted before application. Reconstitution of the microbubbles is not difficult, but it is important to follow the instructions carefully to achieve the optimum effect of the contrast agent.
1. Connect the plunger by screwing it clockwise into the syringe.
2. Open the MiniSpike transfer system from the blister pack and remove the syringe cap.
3. Open the transfer system cap and connect the syringe to the transfer system by screwing it in clockwise.
4. Remove the protective disc from the vial. Insert the vial into the transparent sleeve of the transfer system and press firmly to lock the vial in place.
5. Empty the contents of the syringe into the vial by pushing on the plunger.
6. Shake vigorously for 20 seconds to mix all the contents of the vial into a homogeneous milky liquid.
7. Reverse the system and carefully aspirate SonoVue into the syringe.
8. Unscrew the syringe from the transfer system.
Important: do not use if the liquid obtained is not clear and/or if solid parts of the lyophilizate are visible in the suspension.
SonoVue Video
- Preparation and Reconstitution
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DISCLAIMER
SonoVue should not be administered to patients with known hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.
SonoVue is contraindicated in patients known to have right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure > 90 mmHg), uncontrolled systemic hypertension, and in patients with adult respiratory distress syndrome.
Sonovue should not be used in combination with dobutamine in patients with conditions suggesting cardiovascular instability where dobutamine is contraindicated.
The safety and efficacy of SonoVue have not been established in pregnant and lactating women therefore, SonoVue should not be administered during pregnancy and lactation (see Section 4.6).